Galactose metabolic genes in yeast respond to a ratio of galactose and glucose

Abstract

Natural environments are filled with multiple, often competing, signals. In contrast, biological systems are often studied in "wellcontrolled" environments where only a single input is varied, potentially missing important interactions between signals. Catabolite repression of galactose by glucose is one of the best-studied eukaryotic signal integration systems. In this system, it is believed that galactose metabolic (GAL) genes are induced only when glucose levels drop below a threshold. In contrast, we show that GAL gene induction occurs at a constant external galactose:glucose ratio across a wide range of sugar concentrations. We systematically perturbed the components of the canonical galactose/glucose signaling pathways and found that these components do not account for ratio sensing. Instead we provide evidence that ratio sensing occurs upstream of the canonical signaling pathway and results from the competitive binding of the two sugars to hexose transporters. We show that a mutant that behaves as the classical model expects (i.e., cannot use galactose above a glucose threshold) has a fitness disadvantage compared with wild type. A number of common biological signaling motifs can give rise to ratio sensing, typically through negative interactions between opposing signaling molecules. We therefore suspect that this previously unidentified nutrient sensing paradigm may be common and overlooked in biology.nutrient signaling | signal integration | gene regulation | ratio sensing | yeast

Probabilistic adaptation in changing microbial environments

“…In this model, we assume that cells respond to changes in the environment with a delay, or “lag.” Cells tune to a nutrient at time t and incur a change in growth rate as a consequence of this decision at a later time t  +  k , where k is the lag parameter (we assume here that k  = 1). For growth kinetics, we assume that: (1) cells grow exponentially when their nutrient state matches the environment’s state, (2) there is no switching cost for cells between nutrient states, and (3) when cells are “mismatched” to their environment—i.e., tuned to a nutrient that is not present—their growth rate is zero (this assumption is supported by the observation that cells lacking Gal4, a transcription factor required to activate the GAL pathway, cannot grow in galactose alone (Escalante-Chong et al, 2015)). Altogether, our growth assumptions represent extreme conditions, but they serve as a useful starting point for seeing when an adaptive strategy is beneficial to population growth.…”

“…It has also recently been shown that in environments containing multiple nutrients, cells might be sensitive to complex functions of nutrient levels. Yeast cells decide to turn on the machinery necessary to metabolize galactose (GAL pathway) based on the ratio of glucose to galactose levels in their environment (Escalante-Chong et al, 2015). …”

Adversity magnifies the importance of social information in decision-making

“…A simple and widespread decision rule is to choose options according to the ratio of predicted qualities [28,30,[32][33][34][35][36][37][38][39][40][41]. Then, the probability of choosing option y (P y ) is a monotonically increasing function of the ratio of the estimated probabilities,…”

“…Examples range from bacteria to humans, including rules such as Weber's Law (which depends on the relative difference between qualities (Q y 2 Q x )/(Q y þ Q x )), probability matching (which depends on Q y /(Q x þ Q y )), direct ratio rules (Q y /Q x ) and others [28,30,[32][33][34][35][36][37][38][39][40][41]. All these rules share the condition that…”

Role of the Ubiquitin C-Terminal Hydrolase L1-Modulated Ubiquitin Proteasome System in Auditory Cortex Senescence

“…The control cells were incubated with the abovementioned culture medium. The D -gal-conditioned medium consisted of 2% B27 (Gibco), 1% penicillin-streptomycin, and 4, 8, 12, 16, or 20 mg/mL D -gal in glucose-free DMEM (Gibco) [33,34]. After 72 h or 5 days of D -gal treatment, the culture medium or primary cells were harvested for analysis.…”